1. PLC-beta1 is easily cleaved by calpain and generates a 100-Kda enzyme that lacks the carboxyl-terminal 336 resiudes from Ser-881. The 100-Kda enzyme was catalytically as active as the intact PLC-beta1, but lost the capacity to be activated by alphaq. 2. Two new beta-type PLC isozymes, PLC-beta3 and PLC-beta4, were identified at both protein and DNA levels. 3. Studies of the activation of PLC-beta isozymse by alpha subunits of Gq class G proteins revealed that the extent of activation decreased in the order of PLC-beta1 > PLC-beta3 >> PLC-beta2, suggesting a certain degree of specificity in the interaction of Gqalpha subunits with different PLC-beta isozymes. 4. The beta gamma subunits of G proteins activated the beta-type, but not the gamma-type and delta-type PLC isozymes. The rank order for extent of activation was PLC-beta > PLC-beta2 > PLC-beta1 at all Ca2+ concentrations. The results suggest that beta gamma subunits might represent the active components of the long-sought pertussis-sensitive G proteins. 5. Activation of FcgammaRIII, the receptor responsible for the antibody- dependent cellular cytotoxicity in natural killer cells, is coupled to a nonreceptor protein tyrosine kinase, which phosphorylates and thereby activates PLC-gamma1 and PLC-gamma2. 6. Five members of the src-family tyrosine kinase (lck, lyn, hck, fyn, and src) phosphorylated PLC-gamma1 and PLC-gamma2 in vitro without any distinct specificity between PLC-gamma1 and PLC-gamma2, or between the five kinases. 7. The 47-Kda Nck was shown to be a target for a variety of protein kinases that might modulate the postulated role of Nck as an adaptor for the physical and functional coordination of signaling proteins.